SNRPC promotes triple negative breast cancer progression partially by enhancing TNFAIP2 expression

RNA-binding proteins (RBPs) dysregulation is one of the characteristics of cancer. However, the biological functions and molecular mechanisms of abnormal RBPs in triple-negative breast cancer (TNBC) have not been fully elucidated. In this study, we employed an in vivo CRISPR screen and a TNBC progression model to identify potentially oncogenic RBPs. We identified the small nuclear ribonucleoprotein polypeptide C (SNRPC), a subunit of the U1 small nuclear ribonucleoprotein particle (U1 snRNP), as a key modulator involved in TNBC progression. SNRPC was frequently upregulated and relevant to poor prognosis in TNBC patients. SNRPC ablation significantly impaired the proliferation, migration, and invasion of TNBC cells in vitro and in vivo. Moreover, SNRPC was required for the stability of U1 snRNP, which mediated transcription with splicing. Knockout of SNRPC decreased RNA Pol II enrichment on some oncogenes (TNFAIP2, E2F2 and IGFBP2) and reduced their expression levels by impairing RNA Pol II transcription. We further confirmed that SNRPC deletion will inhibit the TNBC progression partially through the TNFAIP2 Rac1 catenin signal.